title: AdHu5-apoptin induces G2/M arrest and apoptosis in p53-mutated human gastric cancer SGC-7901 cells.
abstract: The use of anticancer therapeutic agents is limited largely by their severe toxicity to normal tissues. The development of novel agents with tumor-specific cell-killing and effective gene delivery properties is thus very desirable. We used human adenovirus serotype 5 (AdHu5) as a vehicle to deliver the apoptin gene to specifically target gastric cancer in a recombinant gene delivery approach. AdHu5-apoptin is a safe and efficacious agent for the treatment of gastric cancer (GC). Our results show that apoptin protein encoded by the apoptin gene delivered via AdHu5 significantly inhibited the proliferation of SGC-7901 GC cells. Apoptin reduced the clone number by more than 75% and resulted in cell cycle arrest in the G2/M phase for 48% of the GC cells. It also induced cleavage of caspase-3, caspase-7, and caspase-9 in the GC cells. Intratumoral and peritumoral in vivo injection of AdHu5-apoptin significantly suppressed tumor growth and induced apoptosis in xenogeneic tumors in mice. The apoptosis induced by AdHu5-apoptin was independent of anti-apoptotic Bcl-2 and Bcl-xL proteins and the p53 pathway. Taken together, our results show that AdHu5-apoptin has great potential as a therapeutic agent for effective treatment of gastric tumors.
authors.affiliation: Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Li
authors.forename: Hongbin
authors.initials: H
authors.lastname: Zhang
authors.forename: Cui
authors.initials: C
authors.lastname: Tan
authors.forename: Weiyan
authors.initials: W
authors.lastname: Peng
authors.forename: Guosheng
authors.initials: G
authors.lastname: Ren
authors.forename: Bei
authors.initials: B
authors.lastname: Jia
authors.forename: Ying
authors.initials: Y
authors.lastname: He
authors.forename: Pilong
authors.initials: P
authors.lastname: Wang
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Zhou
authors.forename: Tingxiu
authors.initials: T
authors.lastname: Xiang
mesh_terms: D000260:Adenoviruses, Human / Q000145:classification / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000235:genetics* / Q000502:physiology; D015153:Blotting, Western; D036022:Capsid Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D059565:G2 Phase Cell Cycle Checkpoints / Q000235:genetics* / Q000502:physiology; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009154:Mutation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012703:Serotyping; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D036022:Capsid Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; C091717:VP3 protein, Chicken anemia virus; D051020:bcl-X Protein; D020169:Caspases